The primary objective of the study is to help elucidate the effects of low-dose aspirin in combination with folic acid on the incidence of live births and spontaneous abortions among a group of women who become pregnant compared to a control group.

Despite the fundamental nature of reproduction, for many it is a process fraught with frustration, inefficiency and imperfections, the effects of which can be severe. Infertility affects 10-15% of couples attempting to conceive. Among all women who conceive, the incidence of spontaneous abortion (SA) has been estimated to be between 15 and 31%, and in many cases the cause is unknown. Additionally, of the four million births yearly in the United States, between 8 and 15% will be born prematurely and experience increased morbidity and mortality as a result. An intervention with even a small absolute effect on any of these outcomes has great implications at the population level due to the large potential attributable benefit.

One such potential intervention is low-dose acetylsalicylic-acid (aspirin). Aspirin has been a primary target of interest because of its anti-inflammatory, vasodilatory and platelet aggregation inhibition properties. To evaluate the effects of low-dose aspirin in combination with folic acid on the incidence of live births and spontaneous abortion, we are conducting a multi-site randomized controlled trial study with two sites and one data coordinating center. Women aged 18-40 currently trying to become pregnant and who have had a single spontaneous abortion in the past year will be eligible for the study. The recruitment goal is 1600 women. Participating women will be randomly assigned to one of two treatment groups. Those randomized to treatment will receive daily low-dose aspirin. Those randomized to placebo will receive daily placebo. Both groups will receive folic acid daily in accordance with recommendations from the U.S. Public Health Service for prevention of birth defects. The duration of treatment regimens (LDA and folic acid or placebo and folic acid) will be 6 menstrual cycles, with those who become pregnant continuing until the end of pregnancy. Monthly urine and blood samples will be collected and questionnaires administered.

Eligibility

Ages Eligible for Study:

18 Years to 40 Years

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Women experiencing one or two pregnancy losses at any point in gestation in the past that were not elective termination(s). At least one of these losses must be well documented by one of the following:

Histologic confirmation of products of conception that were spontaneously passed per vagina or surgically obtained.

Hospital records of fetus delivery.

Late menses and positive serum hCG or positive urine hCG documented by hospital or clinic records followed by either a negative hospital/clinic pregnancy test or a decline in urinary hCG level over 3 days.

Home pregnancy tests without hCG confirmation from a healthcare provider (either serum or urine) will not be accepted.

No more than 5 pregnancies in total including the pregnancy loss(es).*

Up to two prior pregnancies that did not end in a loss.*

*Women may have up to two pregnancies beyond 20 weeks that were not losses, two spontaneous pregnancy losses at any time in the past, and up to one therapeutic or elective termination (two therapeutic or elective terminations if no other pregnancies). Ectopic and molar pregnancies would, for the purpose of enrollment, be considered in the same category as therapeutic termination pregnancies. Women with more than two live births or those with more than two losses, regardless of the week of gestation of the loss, are excluded.

Presence of intact tubes (both), ovaries (both), and uterus.

Between 18 and 40 years of age at time of baseline visit.

Regular menstrual periods between 21 - 42 days in length (within the last 12 months). Regular menstrual periods are defined as no more than an 8-day difference between the woman's shortest and longest cycle.

No more than one missed menses in the past 12 months (other than those missed due to pregnancy or breastfeeding).

Actively trying to conceive with a male partner and not using contraception by the baseline visit.

Not currently pregnant at the baseline or randomization visits.

Ability and willingness to give informed consent.

Willingness to be randomized and to take daily study pills for 6 months to a possible 15 months

Exclusions Criteria:

Known allergies to aspirin or non-steroidal anti-inflammatory agents.

Clinical indication for anticoagulant therapy. These include prior or current thrombosis, antiphospholipid syndrome (APS) or known major thrombophilia.

Clinical indication for chronic use of NSAIDs such as rheumatoid arthritis.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00467363

Locations

United States, Colorado

University of Colorado, Denver School of Medicine, Department of Obstetrics and Gynecology

Denver, Colorado, United States, 80045

United States, New York

Women's Health Research Center, Department of Social and Preventive Medicine, University at Buffalo